Metal-free click cycloadditions of cyclooctynes with azides to give stable 1,2,3-triazoles have found wide utility in labeling glycans, proteins, and lipids of living cells; glycoprotein enrichment for proteomics, protein, and oligonucleotide modification; and tissue reengineering. These reactions, which have been coined “strain-promoted alkyne-azide cycloadditions (SPAAC),” have also made entry in material sciences and have for example been employed for the assembly, cross-linking, and surface modification of dendrimers; derivatization of polymeric nanostructures; and patterning of surfaces.
Despite the apparent utility of reacting an azide with a terminal alkyne, applications in biological systems using this reaction have been practically limited by factors including the undesirable presence of a copper catalyst. Thus, there is a continuing, unmet need for new bioorthogonal reactions.